Glycogenic hepatopathy associated with type 1 diabetes mellitus as a cause of recurrent liver damage

Aminotransferase elevation is a frequent cause of consultation for the Hepatologist, in both the outpatient and inpatient settings, but identifying the origin of these biochemical alterations may be challenging. Here we report a case where acute elevation of aminotransferases, associated with abdominal symptoms, was the cause of two hospitalizations in a short period of time. As the patient suffered from type 1 diabetes, celiac disease, and autoimmune thyroiditis, several potential causes of damage could be hypothesized, including celiac hepatitis, fatty liver, and autoimmune hepatitis. A liver biopsy performed in the occasion of the second hospitalization allowed to rule out autoimmune hepatitis and celiac hepatitis, showing mild signs of fatty infiltration. Staining with periodic acid-Schiff with or without diastase showed a marked accumulation of glycogen, indicating the presence of a glycogenic hepatopathy associated with poorly controlled type 1 diabetes. This condition may be a cause of liver damage in patients with type 1 and occasionally type 2 diabetes, but its occurrence is often overlooked. This case report illustrates the fact that glycogenic hepatopathy may relapse, and prompts the clinician to take into account this condition in the differential diagnosis of causes of liver injury

Reduction of colonic inflammation in HLA-B27 transgenic rats by feeding Marie Ménard apples, rich in polyphenols

Inflammatory bowel diseases (IBD) are immunomediated ailments affecting millions of individuals. Although diet is regarded as an important factor influencing IBD, there are no accepted dietary recommendations presently available. We administered 7.6 % lyophilised apples obtained from two cultivars (Golden Delicious and Marie Ménard, low and high in polyphenols, respectively) to HLA-B27 transgenic rats which develop spontaneous IBD. After 3 months feeding, rats fed Marie Ménard apples had reduced myeloperoxidase activity (3.6 (sem 0.3) v. 2.2 (sem 0.2) U/g tissue; P <0.05) and reduced cyclo-oxygenase-2 (P <0.05) and inducible NO synthase gene expression (P <0.01) in the colon mucosa and significantly less diarrhoea (P <0.05), compared with control rats. Cell proliferation in the colon mucosa was reduced significantly by feeding Golden Delicious apples, with a borderline effect of Marie Ménard apples. Gene expression profiling of the colon mucosa, analysed using the Whole Rat Genome 4 x 44 K Agilent Arrays, revealed a down-regulation of the pathways of PG synthesis, mitogen-activated protein kinase (MAPK) signalling and TNFalpha-NF-kappaB in Marie Ménard-fed rats. In the stools of the animals of this group we also measured a significant reduction of bacteria of the Bacteriodes fragilis group. In conclusion, the administration of Marie Ménard apples, rich in polyphenols and used at present only in the manufacturing of cider, ameliorates colon inflammation in transgenic rats developing spontaneous intestinal inflammation, suggesting the possible use of these and other apple varieties to control inflammation in IBD patient

A mechatronic platform for computer aided detection of nodules in anatomopathological analyses via stiffness and ultrasound measurements

This study presents a platform for ex-vivo detection of cancer nodules, addressing automation of medical diagnoses in surgery and associated histological analyses. The proposed approach takes advantage of the property of cancer to alter the mechanical and acoustical properties of tissues, because of changes in stiffness and density. A force sensor and an ultrasound probe were combined to detect such alterations during force-regulated indentations. To explore the specimens, regardless of their orientation and shape, a scanned area of the test sample was defined using shape recognition applying optical background subtraction to the images captured by a camera. The motorized platform was validated using seven phantom tissues, simulating the mechanical and acoustical properties of ex-vivo diseased tissues, including stiffer nodules that can be encountered in pathological conditions during histological analyses. Results demonstrated the platform’s ability to automatically explore and identify the inclusions in the phantom. Overall, the system was able to correctly identify up to 90.3% of the inclusions by means of stiffness in combination with ultrasound measurements, paving pathways towards robotic palpation during intraoperative examinations

hERG1 Potassium Channel Expression in Colorectal Adenomas: Comparison with Other Preneoplastic Lesions of the Gastrointestinal Tract

Preneoplastic lesions represent a useful target for early diagnosis and follow-up of gastrointestinal malignancies. hERG1 channel expression was tested by immunohistochemistry (IHC) in a cohort of colorectal adenoma samples belonging to Italian subjects. Overall, hERG1 was expressed in 56.5% of cases with both high staining intensity and a high percentage of positive cells. Moreover, hERG1 was expressed in a higher percentage of dysplastic adenomas with respect to hyperplastic lesions, and the proportion of positive samples further increased in patients with high-grade dysplasia. Comparing hERG1 expression in other preneoplastic lesions of the GI tract (gastric dysplasia and Barrett’s esophagus), it emerged that in all the conditions, hERG1 was expressed with a diffused pattern, throughout the cell, with variable staining intensity within the samples. The highest expression was detected in gastric dysplasia samples and the lowest in Barrett’s esophagus at similar levels observed in colorectal adenomas. Our results show that hERG1 is aberrantly expressed in human preneoplastic lesions of the gastrointestinal tract and has a different pattern of expression and role in the different sites. Overall, the detection of hERG1 expression in preneoplastic lesions could represent a novel diagnostic or prognostic marker of progression in the gastrointestinal tract

Herg1 gene and HERG1 protein are overespressed in colorectal cancers and regulate cell invasion of tumor cells

The acquisition of the capacity to invade surrounding tissues confers a more malignant phenotype to tumor cells and is necessary for the establishment of metastases. The understanding of the molecular mechanisms underlying cell invasion in human solid tumors such as colorectal cancers could provide not only more sensitive prognostic analyses but also novel molecular targets for cancer therapy.We report in this article that K+ ion channels belonging to the HERG family are important determinants for the acquisition of an invasive phenotype in colorectal cancers. The herg1 gene and HERG1 protein are expressed in many colon cancer cell lines, and the activity of HERG channels modulates colon cancer cell invasiveness. Moreover, the amount of HERG1 protein expressed on the plasma membrane is directly related to the invasive phenotype of colon cancer cells.Finally, both the herg1 gene and HERG1 protein were expressed in a high percentage of primary human colorectal cancers, with the highest incidence occurring in metastatic cancers, whereas no expression could be detected either in normal colonic mucosa or in adenomas